P‐Wave Duration Is Associated With Aging Patterns in Structural Brain Networks

Figures

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  Figure 1. Inclusion flow chart. Self‐reported noncancer illness codes (1082, 1083, 1240, 1244, 1245, 1246, 1247, 1256, 1258, 1259, 1261, 1262, 1263, 1264, 1266, 1289, 1397, 1425, 1433, 1659) and ICD‐10 codes for dementia and Parkinson disease. BMI indicates body mass index; ICD‐10, International Classification of Diseases, Tenth Revision; and MI, myocardial infarction.

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  Figure 2. Methodological overview of BAI extraction. T1w brain aging features including cortical thickness and gray/white matter intensity ratio were inputs into a graph convolutional network resulting in a fully connected layer and predicted “brain age” outputs. Chronological age was subtracted from predicted brain age resulting in 12 regional BAIs. Chronological age was regressed out from each BAI and used for analysis. Linear modeling was performed with PWD as a predictor variable while correcting for possible confounders by including them as covariates. PWD represents the current moving from the sinoatrial node to the atrioventricular node and characterizes atrial depolarization. Created in BioRender.com. AD indicates Alzheimer disease; BAI, brain age index; CT, cortical thickness; GW IR, gray/white matter intensity ratio; MRI, magnetic resonance imaging; and ReLU, rectified linear unit.

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  Figure 3. P‐wave duration plotted against age and stratified by sex. Colors denote P‐wave duration percentiles listed on the left side. Density plots across ages for each sex are depicted atop the scatters. Density plot on the right displays P‐wave duration for male participants (dashed line) and female participants (solid line). Note higher densities of both high and low P‐wave duration at older ages and across both sexes. Male participants tended to have longer P‐wave duration whereas female participants favored shorter.

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  Figure 4. BAI associations with PWD. A, T‐statistics of regional BAI (overlapping) associated with PWD. B, Standardized coefficients of PWD and all other regression coefficients (with the exception of the 4 MRI PCA components explaining 88.3% of scanner related variance) from all 12 models (whole brain BAI, AD signature region BAI, and 10 regional BAI). Shorter P‐wave duration was associated with a higher brain age. Regional BAI that survived multiple comparisons included the frontoparietal, dorsal attention, and ventral attention (middle panel), as well as the sensorimotor and language networks (right panel). Covariates associated with a higher BAI include hypertension, diabetes, smoking status, and frequent alcohol consumption. Covariates associated with a lower BAI include a higher bone mineral density T‐score, having a college education, and younger age. Filled points indicate effects that survived multiple comparisons correction across all 12 BAIs (within each covariate). AD indicates Alzheimer disease; ApoE4, apolipoprotein E4; BAI, brain age index; FDR, false discovery rate; MRI, magnetic resonance imaging; ns, not significant; PCA, principal component analysis; and PWD, P‐wave…

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  Figure 5. Regional BAI associations with composite cognitive measures—average memory, executive function, processing speed, reasoning, and total cognition. Values displayed are standardized regression coefficients. All models included age, sex, college attendance, and 4 MRI scanner PCA components (explaining 88.3% of scanner related variance) as covariates. Higher cognitive scores were generally associated with a lower brain age. Filled shape styles indicate varying levels of significance that survived multiple comparisons correction across all 5 cognitive measures and all 12 BAI indices combined. AD indicates Alzheimer's disease; BAI, brain age index; FDR, false discovery rate; MRI, magnetic resonance imaging; ns, not significant; and PCA, principal component analysis.